The injection of naked DNA capable of expressing a viral protein in muscles of rodents and nonhuman primates has been shown to induce a specific immune response against that viral protein. Since conventional vaccine candidates have proven ineffective in generating protective immunity against human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV), an expression plasmid encoding the gag protein of SIV was generated. In transient transfection assays, this expression plasmid is capable of producing SIV gag protein and SIV reverse transcriptase activity. To evaluate whether direct injection of this expression plasmid in muscle can induce an immune response against SIV gag, we initiated DNA injection studies in the muscles of mice. The injection of a control reporter gene containing plasmid in muscles of mice demonstrated that DNA injection can result in the expression of the reporter gene. Studies thus far have not demonstrated that this expression plasmid can promote an immune response in mice following DNA injections. As expression from DNA may be dependent upon each batch of plasmid DNA, these studies will be repeated. If induction of an immune response can be demonstrated in mice, studies in nonhuman primates will be initiated.